tbuckley/cabot-search huggingface dataset:
Highly pathogenic avian influenza A(H5N1) virus infection in foxes with PB2-M535I identified as a novel mammalian adaptation, Northern Ireland, July 2023
Authors: Paula Lagan, Robyn McKenna, Salam Baleed, Bob Hanna, Jason Barley, Shirley McConnell, Anastasia Georgaki, Tarja Sironen, Ari Kauppinen, Tuija Gadd, Erika Lindh, Niina Ikonen, Michael J McMenamy, Ken Lemon
Journal: Eurosurveillance (2023)

We report cases of mammalian infection with highly pathogenic avian influenza (HPAI) virus A(H5N1) clade 2.3.4.4b in Northern Ireland. Two common gulls ( Larus canus ) and two red fox kits ( Vulpes vulpes ), were found dead in close vicinity. Comparison of viral whole genome sequences obtained from the animals identified a novel mammalian adaptation, PB2-M535I. Analysis of genetic sequences from other recent mammalian infections shows that this mutation has arisen on at least five occasions in three European countries since April 2023.
Prognostic Significance of Different Ventricular Ectopic Burdens During Submaximal Exercise in Asymptomatic UK Biobank Subjects
Authors: Stefan van Duijvenboden, Julia Ramírez, Michele Orini, Nay Aung, Steffen E. Petersen, Aiden Doherty, Andrew Tinker, Patricia B. Munroe, Pier D. Lambiase
Journal: Circulation (2023)

The consequences of exercise-induced premature ventricular contractions (PVCs) in asymptomatic individuals remain unclear. This study aimed to assess the association between PVC burdens during submaximal exercise and major adverse cardiovascular events (MI/HF/LTVA: myocardial infarction [MI], heart failure [HF], and life-threatening ventricular arrhythmia [LTVA]), and all-cause mortality. Additional end points were MI, LTVA, HF, and cardiovascular mortality.
Performance of Thrombectomy-Capable, Comprehensive, and Primary Stroke Centers in Reperfusion Therapies for Acute Ischemic Stroke: Report From the Get With The Guidelines–Stroke Registry
Authors: Radoslav Raychev, Jie-Lena Sun, Lee Schwamm, Eric E. Smith, Gregg C. Fonarow, Steven R. Messé, Ying Xian, Karen Chiswell, Rosalia Blanco, Brian Mac Grory, Jeffrey L. Saver
Journal: Circulation (2023)

BACKGROUND: The thrombectomy-capable stroke center (TSC) is a recently introduced intermediate tier of accreditation for hospitals at which patients with acute ischemic stroke receive care. The comparative quality and clinical outcomes of reperfusion therapies at TSCs, primary stroke centers (PSCs), and comprehensive stroke centers (CSCs) have not been well delineated. METHODS: We conducted a retrospective, observational, cohort study from 2018 to 2020 that included patients with acute ischemic stroke who received endovascular thrombectomy (EVT) and intravenous thrombolysis reperfusion therapies at CSCs, TSCs, or PSCs. Participants were recruited from Get With The Guidelines–Stroke registry. Study end points included timeliness of intravenous thrombolysis and EVT, successful reperfusion, discharge destination, discharge mortality, and functional independence at discharge. RESULTS: Among 84 903 patients, 48 682 received EVT, of whom 73% were treated at CSCs, 22% at PSCs, and 4% at TSCs. The median annual EVT volume was 76 for CSCs, 55 for TSCs, and 32 for PSCs. Patient differences by center status included higher National Institutes of Health Stroke Scale score, longer onset-to-arrival time, and higher transfer-in rates for CSCs, TSCs, and PSCs, respectively. In adjusted analyses, the likelihood of achieving the goal door-to-needle time was higher in CSCs compared with PSCs (odds ratio [OR], 1.39 [95% CI, 1.17–1.66]) and in TSCs compared with PSCs (OR, 1.45 [95% CI, 1.08–1.96]). Likewise, the odds of achieving the goal door-to-puncture time were higher in CSCs compared with PSCs (OR, 1.58 [95% CI, 1.13–2.21]). CSCs and TSCs also demonstrated better clinical efficacy outcomes compared with PSCs. The odds of discharge to home or rehabilitation were higher in CSCs compared with PSCs (OR, 1.18 [95% CI, 1.06–1.31]), whereas the odds of in-hospital mortality or discharge to hospice were lower in both CSCs compared with PSCs (OR, 0.87 [95% CI, 0.81–0.94]) and TSCs compared with PSCs (OR, 0.86 [95% CI, 0.75–0.98]). There were no significant differences in any of the quality-of-care metrics and clinical outcomes between TSCs and CSCs. CONCLUSIONS: In this study representing national US practice, CSCs and TSCs exceeded PSCs in key quality-of-care reperfusion metrics and outcomes, whereas TSCs and CSCs demonstrated a similar performance. With more than one-fifth of all EVT procedures during the study period conducted at PSCs, it may be desirable to explore national initiatives aimed at facilitating the elevation of eligible PSCs to a higher certification status.
Location and Types of Treatment for Prostate Cancer After the Veterans Choice Program Implementation
Authors: Bradley A. Erickson, Richard M. Hoffman, Jason Wachsmuth, Vignesh T. Packiam, Mary S. Vaughan-Sarrazin
Journal: JAMA Network Open (2023)

Importance The Veterans Choice Program (VCP) was implemented in 2014 to help veterans gain broader access to specialized care outside of the Veterans Health Administration (VHA) facilities by providing them with purchased community care (CC). Objective To describe the prevalence and patterns in VCP-funded purchased CC after the implementation of the VCP among veterans with prostate cancer. Design, Setting, and Participants This cohort study used VHA administrative data on veterans with prostate cancer diagnosed between January 1, 2015, and December 31, 2018. These veterans were regular VHA primary care users. Analyses were performed from March to July 2023. Exposures Driving distance (in miles) from residence to nearest VHA tertiary care facility. The location (VHA or purchased CC) in which treatment decisions were made was ascertained by considering 3 factors: (1) location of the diagnostic biopsy, (2) location of most of the postdiagnostic prostate-specific antigen laboratory testing, and (3) location of most of the postdiagnostic urological care encounters. Main Outcomes and Measures The main outcome was receipt of definitive treatment and proportion of purchased CC by treatment type (radical prostatectomy [RP], radiotherapy [RT], or active surveillance) and by distance to nearest VHA tertiary care facility. Quality was evaluated based on receipt of definitive treatment for Gleason grade group 1 prostate cancer (low risk/limited treatment benefit by guidelines). Results The cohort included 45 029 veterans (mean [SD] age, 67.1 [6.9] years) with newly diagnosed prostate cancer; of these patients, 28 866 (64.1%) underwent definitive treatment. Overall, 56.8% of patients received definitive treatment from the purchased CC setting, representing 37.5% of all RP care and 66.7% of all RT care received during the study period. Most patients who received active surveillance management (92.5%) remained within the VHA. Receipt of definitive treatment increased over the study period (from 5830 patients in 2015 to 9304 in 2018), with increased purchased CC for patients living farthest from VHA tertiary care facilities. The likelihood of receiving definitive treatment of Gleason grade group 1 prostate cancer was higher in the purchased CC setting (adjusted relative risk ratio, 1.79; 95% CI, 1.65-1.93). Conclusions and Relevance This cohort study found that the percentage of veterans receiving definitive treatment in VCP-funded purchased CC settings increased significantly over the study period. Increased access, however, may come at the cost of low care quality (overtreatment) for low-risk prostate cancer.
A Daunting and Challenging Task to Prove the Effectiveness of Reducing Acute Exacerbation in COPD Patients with Type 2 Diabetes by GLP-1 Receptor Agonists
Authors: Qiumeng Li, Yating Chen, Hang Jiang, Yue Xi, Jiahe Wang, Xiaofeng Zhu, Jianxiong Lai, Nuofu Zhang, Dongxing Zhao
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"A Daunting and Challenging Task to Prove the Effectiveness of Reducing Acute Exacerbation in COPD Patients with Type 2 Diabetes by GLP-1 Receptor Agonists." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Emergence and rapid dissemination of highly resistant NDM-14-producing Klebsiella pneumoniae ST147, France, 2022
Authors: Cécile Emeraud, Aba Mahamat, Agnès B. Jousset, Sandrine Bernabeu, Tania Goncalves, Camille Pommier, Delphine Girlich, Aurélien Birer, Christophe Rodriguez, Jean-Michel Pawlotsky, Thierry Naas, Rémy A. Bonnin, Laurent Dortet
Journal: Eurosurveillance (2023)

Background Since 2021, an emergence of New Delhi metallo-β-lactamase (NDM)-14-producing Klebsiella pneumoniae has been identified in France. This variant with increased carbapenemase activity was not previously detected in Enterobacterales. Aim We investigated the rapid dissemination of NDM-14 producers among patients in hospitals in France. Methods All NDM-14-producing non-duplicate clinical isolates identified in France until June 2022 (n = 37) were analysed by whole genome sequencing. The phylogeny of NDM-14-producers among all K. pneumoniae sequence type (ST) 147 reported in France since 2014 (n = 431) was performed. Antimicrobial susceptibility testing, conjugation experiments, clonal relationship and molecular clock analysis were performed. Results The 37 NDM-14 producers recovered in France until 2022 belonged to K. pneumoniae ST147. The dissemination of NDM-14-producing K. pneumoniae was linked to a single clone, likely imported from Morocco and responsible for several outbreaks in France. The gene bla NDM-14 was harboured on a 54 kilobase non-conjugative IncFIB plasmid that shared high homology with a known bla NDM-1 -carrying plasmid. Using Bayesian analysis, we estimated that the NDM-14-producing K. pneumoniae ST147 clone appeared in 2020. The evolutionary rate of this clone was estimated to 5.61 single nucleotide polymorphisms per genome per year. The NDM-14 producers were highly resistant to all antimicrobials tested except to colistin, cefiderocol (minimum inhibitory concentration 2 mg/L) and the combination of aztreonam/avibactam. Conclusion Highly resistant NDM-14 producing K. pneumoniae can rapidly spread in healthcare settings. Surveillance and thorough investigations of hospital outbreaks are critical to evaluate and limit the dissemination of this clone.
Recombinant PreS‐fusion protein vaccine for birch pollen and apple allergy
Authors: Musa Khaitov, Igor Shilovskiy, Rudolf Valenta, Milena Weber, Artem Korneev, Inna Tulaeva, Pia Gattinger, Marianne van Hage, Gerhard Hofer, Jon R. Konradsen, Walter Keller, Oluwatoyin Akinfenwa, Alina Poroshina, Nataliya Ilina, Elena Fedenko, Olga Elisyutina, Alla Litovkina, Evgenii Smolnikov, Aleksandra Nikonova, Sergei Rybalkin, Vladimir Aldobaev, Valeriy Smirnov, Nadezhda Shershakova, Olga Petukhova, Dmitriy Kudlay, Artem Shatilov, Anastasiya Timofeeva, Raffaela Campana, Sergei Udin, Veronica Skvortsova
Journal: Allergy (2023)

Abstract Background IgE cross‐sensitization to major birch pollen allergen Bet v 1 and pathogenesis‐related (PR10) plant food allergens is responsible for the pollen‐food allergy syndrome. Methods We designed a recombinant protein, AB‐PreS, consisting of non‐allergenic peptides derived from the IgE‐binding sites of Bet v 1 and the cross‐reactive apple allergen, Mal d 1, fused to the PreS domain of HBV surface protein as immunological carrier. AB‐PreS was expressed in E. coli and purified by chromatography. The allergenic and inflammatory activity of AB‐PreS was tested using basophils and PBMCs from birch pollen allergic patients. The ability of antibodies induced by immunization of rabbits with AB‐PreS and birch pollen extract‐based vaccines to inhibit allergic patients IgE binding to Bet v 1 and Mal d 1 was assessed by ELISA. Results IgE‐binding experiments and basophil activation test revealed the hypoallergenic nature of AB‐PreS. AB‐PreS induced lower T‐cell activation and inflammatory cytokine production in cultured PBMCs from allergic patients. IgG antibodies induced by five injections with AB‐PreS inhibited allergic patients' IgE binding to Bet v 1 and Mal d 1 better than did IgG induced by up to 30 injections of six licensed birch pollen allergen extract‐based vaccines. Additionally, immunization with AB‐PreS induced HBV‐specific antibodies potentially protecting from infection with HBV. Conclusion The recombinant AB‐PreS‐based vaccine is hypoallergenic and superior over currently registered allergen extract‐based vaccines regarding the induction of blocking antibodies to Bet v 1 and Mal d 1 in animals.
Industrialized human gut microbiota increases CD8+ T cells and mucus thickness in humanized mouse gut
Authors: Pajau Vangay, Tonya Ward, Sarah Lucas, Lalit K. Beura, Dominique Sabas, Max Abramson, Lisa Till, Susan L. Hoops, Purna Kashyap, Ryan C. Hunter, David Masopust, Dan Knights
Journal: Gut Microbes (2023)

Immigration to a highly industrialized nation has been associated with metabolic disease and simultaneous shifts in microbiota composition, but the underlying mechanisms are challenging to test in human studies. Here, we conducted a pilot study to assess the differential effects of human gut microbiota collected from the United States (US) and rural Thailand on the murine gut mucosa and immune system. Colonization of germ-free mice with microbiota from US individuals resulted in an increased accumulation of innate-like CD8 T cells in the small intestine lamina propria and intra-epithelial compartments when compared to colonization with microbiota from Thai individuals. Both TCRγδ and CD8αα T cells showed a marked increase in mice receiving Western microbiota and, interestingly, this phenotype was also associated with an increase in intestinal mucus thickness. Serendipitously, an accidentally infected group of mice corroborated this association between elevated inflammatory response and increased mucus thickness. These results suggest that Western-associated human gut microbes contribute to a pro-inflammatory immune response.
Factors Associated With Vaccination Refusal—Critical Lessons From the Omicron Wave in Hong Kong
Authors: Leonard Hofstra, Heidi J. Larson
Journal: JAMA Network Open (2023)

Phyllis Lun, MA; Ke Ning, PhD; Yishan Wang, MSc; Tiffany S. W. Ma, MSc; Francis P. Flores, BSc; Xiao Xiao, MStat; Mythily Subramaniam, MD, PhD; Edimansyah Abdin, PhD; Linwei Tian, PhD; Tim K. Tsang, PhD; Kathy Leung, PhD; Joseph T. Wu, PhD; Benjamin J. Cowling, PhD; Gabriel M. Leung, MD; Michael Y. Ni, MD
Cancers Attributable to Infections in the US in 2017
Authors: Karena D. Volesky-Avellaneda, Samantha Morais, Stephen D. Walter, Thomas R. O’Brien, Allan Hildesheim, Eric A. Engels, Mariam El-Zein, Eduardo L. Franco
Journal: JAMA Oncology (2023)

Infections are largely modifiable causes of cancer. However, there remains untapped potential for preventing and treating carcinogenic infections in the US.
Developmental Trajectory of Body Weight in Youths at Risk for Major Mood Disorders
Authors: Nitya Adepalli, Jill Cumby, Niamh Campbell, Barbara Pavlova, Martin Alda, Leah E. Cahill, Rudolf Uher
Journal: JAMA Network Open (2023)

Mood disorders are associated with increased body weight, especially in females, but it remains unknown when the weight increase starts.To examine sex-specific weight trajectories associated with familial mood disorder risk and determine the age at which youth at familial risk for mood disorders begin to diverge in weight from controls.This community-based, single-center, acceleration cohort study of youth at familial risk for mood disorders and controls with yearly follow-ups (mean [SD], 5 [2.1] years) from January 1, 2014, to December 31, 2022, assessed 394 unaffected female and male offspring (aged 3 to 20 years) of parents with or without a mood disorder. Parents with mood (depressive or bipolar) disorders were recruited through adult mental health services. Parents of control participants were matched on age and socioeconomic factors and recruited through acquaintance referrals or schools.The youth in the familial mood risk group had at least 1 parent with a major mood disorder, whereas control youth did not have a parent with a mood disorder.Body mass indexes (BMIs) were calculated as weight in kilograms divided by height in meters squared from measured weight and height at annual assessments and then converted to age- and sex-adjusted z scores (zBMIs). Repeated-measure regressions examined the association between zBMI and age in youth at familial risk of mood disorders and controls while accounting for sex. Sensitivity analyses accounted for socioeconomic status, prematurity, and birth weight.Of 394 participants (mean [SD] age, 11.5 [3.6] years; 203 [51.5%] female), youths at familial risk for mood disorders showed overall no difference in body weight (β = 0.12; 95% CI, 0.01-0.24) from controls. A sex-specific difference was detected, with females at familial risk showing a rapid peripubertal increase in body weight, leading to significantly increased zBMIs at 12 years and older compared with controls (β = 0.57; 95% CI, 0.31-0.82) independent of socioeconomic status, prematurity, or birth weight. Males did not differ from controls at any age.In this cohort study, females with a family history of mood disorders were prone to weight gain starting around puberty and predating mood disorder onset. Early interventions aiming to prevent adverse mental and physical outcomes in this vulnerable group need to start in childhood.
Hypoxia-Induced Neuronal Activity in Glioma Patients Polarizes Microglia by Potentiating RNA m6A Demethylation
Authors: Xiaofan Guo, Wei Qiu, Boyan Li, Yanhua Qi, Shaobo Wang, Rongrong Zhao, Bo Cheng, Xiao Han, Hao Du, Ziwen Pan, Shulin Zhao, Jiawei Qiu, Gang Li, Hao Xue
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Neuronal activity in the brain has been reported to promote the malignant progression of glioma cells via nonsynaptic paracrine and electrical synaptic integration mechanisms. However, the interaction between neuronal activity and the immune microenvironment in glioblastoma (GBM) remains largely unclear. Experimental Design: By applying chemogenetic techniques, we enhanced and inhibited neuronal activity in vitro and in a mouse model to study how neuronal activity regulates microglial polarization and affects GBM progression. Results: We demonstrate that hypoxia drove glioma stem cells (GSC) to produce higher levels of glutamate, which activated local neurons. Neuronal activity promoted GBM progression by facilitating microglial M2 polarization through enriching miR-200c-3p in neuron-derived exosomes, which decreased the expression of the m6A writer zinc finger CCCH-type containing 13 (ZC3H13) in microglia, impairing methylation of dual specificity phosphatase 9 (DUSP9) mRNA. Downregulation of DUSP9 promoted ERK pathway activation, which subsequently induced microglial M2 polarization. In the mouse model, cortical neuronal activation promoted microglial M2 polarization whereas cortical neuronal inhibition decreased microglial M2 polarization in GBM xenografts. miR-200c-3p knockdown in cortical neurons impaired microglial M2 polarization and GBM xenograft growth, even when cortical neurons were activated. Treatment with the anti-seizure medication levetiracetam impaired neuronal activation and subsequently reduced neuron-mediated microglial M2 polarization. Conclusions: These findings indicated that hypoxic GSC-induced neuron activation promotes GBM progression by polarizing microglia via the exosomal miR-200c-3p/ZC3H13/DUSP9/p-ERK pathway. Levetiracetam, an antiepileptic drug, blocks the abnormal activation of neurons in GBM and impairs activity-dependent GBM progression. See related commentary by Cui et al., p. 1073
Membrane barriers for guided bone regeneration: An overview of available biomaterials
Authors: Gabriel Mizraji, Alon Davidzohn, Mervi Gursoy, Ulvi K. Gursoy, Lior Shapira, Asaf Wilensky
Journal: Periodontology 2000 (2023)

Dental implants revolutionized the treatment options for restoring form, function, and esthetics when one or more teeth are missing. At sites of insufficient bone, guided bone regeneration (GBR) is performed either prior to or in conjunction with implant placement to achieve a three-dimensional prosthetic-driven implant position. To date, GBR is well documented, widely used, and constitutes a predictable and successful approach for lateral and vertical bone augmentation of atrophic ridges. Evidence suggests that the use of barrier membranes maintains the major biological principles of GBR. Since the material used to construct barrier membranes ultimately dictates its characteristics and its ability to maintain the biological principles of GBR, several materials have been used over time. This review, summarizes the evolution of barrier membranes, focusing on the characteristics, advantages, and disadvantages of available occlusive barrier membranes and presents results of updated meta-analyses focusing on the effects of these membranes on the overall outcome.
Normal B cells express <scp>ZAP70</scp> in chronic lymphocytic leukemia: A link between autoimmunity and lymphoproliferation?
Authors: Dana Ghergus, Mickaël Martin, Anne‐Marie Knapp, Fabien Delmotte, Aurélie Joublin‐Delavat, Sophie Jung, Jean‐Nicolas Schickel, Isabelle Mendel, Arnaud Dupuis, Bernard Drénou, Hervé Ghesquières, Gilles Salles, Lucile Baseggio, Raoul Herbrecht, Anne‐Sophie Korganow, Laurent Vallat, Pauline Soulas‐Sprauel, Eric Meffre, Thierry Martin
Journal: American Journal of Hematology (2023)

Abstract ZAP70 has a prognostic value in chronic lymphocytic leukemia (CLL), through altered B‐cell receptor signaling, which is important in CLL pathogenesis. A good correlation between ZAP70 expression in CLL cells and the occurrence of autoimmune phenomena has been reported. Yet, the great majority of CLL‐associated autoimmune cytopenia is due to polyclonal immunoglobulin (Ig) G synthesized by nonmalignant B cells, and this phenomenon is poorly understood. Here, we show, using flow cytometry, that a substantial percentage of CD5‐ nonmalignant B cells from CLL patients expresses ZAP70 compared with CD5‐ B cells from healthy subjects. This ZAP70 expression in normal B cells from CLL patients was also evidenced by the detection of ZAP70 mRNA at single‐cell level with polyclonal Ig heavy‐ and light‐chain gene transcripts. ZAP70+ normal B cells belong to various B‐cell subsets and their presence in the naïve B‐cell subset suggests that ZAP70 expression may occur during early B‐cell development in CLL patients and potentially before malignant transformation. The presence of ZAP70+ normal B cells is associated with autoimmune cytopenia in CLL patients in our cohort of patients, and recombinant antibodies produced from these ZAP70+ nonmalignant B cells were frequently autoreactive including anti‐platelet reactivity. These results provide a better understanding of the implication of ZAP70 in CLL leukemogenesis and the mechanisms of autoimmune complications of CLL.
Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients
Authors: Sam M. Murray, Elisa Pose, Melanie Wittner, Maria-Carlota Londoño, Golda Schaub, Jonathan Cook, Stavros Dimitriadis, Georgina Meacham, Sophie Irwin, Zixiang Lim, Paul Duengelhoef, Martina Sterneck, Ansgar W. Lohse, Valeria Perez, Palak Trivedi, Khush Bhandal, Benjamin H. Mullish, Pinelopi Manousou, Nicholas M. Provine, Emma Avitabile, Miles Carroll, Tom Tipton, Saoirse Healy, Patrizia Burra, Paul Klenerman, Susanna Dunachie, Barbara Kronsteiner, Agnieszka Katarzyna Maciola, Giulia Pasqual, Virginia Hernandez-Gea, Juan Carlos Garcia-Pagan, Pietro Lampertico, Massimo Iavarone, Pere Gines, Marc Lütgehetmann, Julian Schulze zur Wiesch, Francesco Paolo Russo, Eleanor Barnes, Thomas Marjot
Journal: Journal of Hepatology (2023)

Comparative assessments of immunogenicity following different COVID-19 vaccines in patients with distinct liver diseases are lacking. SARS-CoV-2-specific T-cell and antibody responses were evaluated longitudinally after one to three vaccine doses, with long-term follow-up for COVID-19-related clinical outcomes.